Inheritance of Blood Groups

In this section, we will briefly describe several general principles that apply to how most blood groups are inherited.

Most blood group genes are co-dominant. For example, in the ABO system, A and B genes are co-dominant; in the Rh system, C and c are co-dominant; and in the Kell system, K and k are co-dominant. Unlike in classical genetics, the capital and lowercase letters do not denote dominant and recessive alleles, respectively. Examples of dominant/recessive gene pairs include Le and le and H and h. Almost all blood group genes are inherited on the autosomes.

Many blood group antigens are indirect gene products. For example, A and B antigens are carbohydrates. Their genes produce proteins (enzymes) called transferases which transfer sugars from carrier molecules to acceptor molecules. Antigen specificities then reside in the terminal sugars that are added. These antigens have to be made indirectly because genes can only directly produce proteins. Usually if a gene is present, its corresponding antigen will be present.

Sometimes blood group antigens result from gene interaction in which several genes combine to produce a red cell phenotype. An example is the interaction of H, Le, and Se genes to produce the antigens of the Lewis BGS.

There are three mechanisms that can result in blood group antigens not being produced. Blood group genes may not make their antigens because they are amorphs or silent genes, which either do not make proteins or make proteins having no transferase activity, e.g., the O gene in the ABO system does not make an antigen because it has no transferase activity. In other cases blood group genes do not produce their antigens because of rare suppressor or regulatory genes inherited at a different locus, e.g., in the Rh system one type of Rh null (a rare phenotype that lacks Rh antigens) results from suppressor genes that do not allow the functional Rh genes to produce their antigen products. Thus suppressor genes can cause deleted phenotypes in which antigens that are normally present are absent. Also, in rare cases blood group genes that are normally present may be lost by the process of deletion, in which part of the chromosome carrying the gene is lost.

In a nutshell

Most blood group genes are co-dominant and located on autosomes. Many genes make antigens indirectly by producing transferases that add single terminal sugars, which determine antigen specificity. Sometimes blood group genes are not expressed due to amorphic genes, suppressor genes, or gene deletions.